Hormone replacement therapy (HRT), in the form of estrogen replacement therapy (ERT), was widely used in the 1960s and 1970s. In the mid 1970s epidemiologic studies demonstrated that ERT use significantly increased endometrial cancer risk. Recent population-based studies have shown that breast cancer risk may also be increased, although to a much lesser extent. These risks of ERT use have to be balanced against, the clear beneficial effects of ERT in reducing certain menopausal symptoms and osteoporosis, and, most importantly, probably coronary heart disease (CHD) risk. In response to the endometrial cancer risk a progestogen is now commonly added for the last 10-14 days of the 28-day ERT cycle (estrogen-progestogen replacement therapy, EPRT). Part of the beneficial effect of ERT on CHD may be lost with EPRT, and it may be argued that the breast cancer risk may be increased. EPRT use will cause less endometrial cancer than ERT, but it is not clear that EPRT use will be associated with less endometrial cancer than no HRT; certain lines of argument suggest that EPRT use will cause a significant increase in endometrial cancer risk. As EPRT increases in popularity, it is clearly important, both from a public health standpoint and to increase our understanding of carcinogenic and other disease processes, to monitor its effects on endometrial cancer, breast cancer and CHD risk, and possibly other disease endpoints. Given the probable adverse effect of progestogen on the CHD component of the risk-benefit equation, the effect of estrogen-progestogen therapy on endometrial cancer and breast cancer risk is crucial in determining whether widespread use of such therapy is justified. This proposed case-control study of 920 endometrial cancer cases age 55-64 and 920 matched neighborhood controls addresses the endometrial cancer issue. In-person structured interviews will be conducted: to facilitate recall, a photograph album of all ERT and EPRT preparations ever sold will be used. All cases will have their pathology slides blindly reviewed by a single pathologist to attain uniformity of diagnosis and to allow subgroup analysis of the results by certainty of diagnosis and extent of disease. We will also assess the relationships of endometrial cancer to smoking, diet and physical activity.